Akt-Induced Phosphorylation of N-CoR at Serine 1450 Contributes to Its Misfolded Conformational Dependent Loss (MCDL) in Acute Myeloid Leukemia of the M5 Subtype

10.1371/journal.pone.0070891PLoS ONE88-POLN

Gastrointestinal Tolerability and Absorption of R‐

We compared the gastrointestinal (GI) tolerability and assessed for bioequivalent absorption of R-lipoic acid (LA) in people with progressive multiple sclerosis (MS) in a single-center, double-blind, randomized crossover trial. Participants randomly assigned to formulation sequence took 600Â mg of R-LA or 1200Â mg of a 1:1 racemic R,S-LA mixture in single daily doses for 7 to 10 days, underwent a washout of at least 7 days, and then took the other form of LA for 7 to 10 days. At the end of each period on LA, GI symptoms were assessed with GI questions from the Monitoring of Side Effects Scale. Serum LA concentrations were measured before and 60, 90, 120, 180, and 240 minutes after the first and last day\u27s dose of each form of LA to derive an area under the plasma concentration-time curve (AUC) and maximum serum concentration (Cmax ). Twenty participants enrolled (12 women; 15 secondary progressive MS, 5 primary progressive MS; mean age, 59.6 years). Two withdrew early due to symptoms while taking R,S-LA, and one withdrew early while taking R-LA. The mean GI Monitoring of Side Effects Scale score was 1.7 points lower on R-LA than on R,S-LA (P = .069), and there were fewer reports of each GI side effect when taking the R-LA than the R,S-LA (31 vs 60; P = .025). The AUC and Cmax for R-LA were bioequivalent for the 2 formulations (90% confidence intervals 97.4% to 99.3% for AUC and 93.4% to 98.2% for Cmax ). This study supports that in people with progressive MS, there is better GI tolerability and bioequivalent serum absorption of R-LA when 600Â mg of R-LA is taken as R-LA alone than when taken in a 1:1 racemic R,S-LA mixture

Immunomodulatory activities of alpha lipoic acid with a special focus on its efficacy in preventing miscarriage

Introduction: Alpha lipoic acid (ALA) is an essential mitochondrial co-factor and, as a free molecule, it can exert multi-level immunomodulatory functions. Both ALA and its reduced form, dihydrolipoic acid (DHLA), are believed to be able to chelate heavy metals, to regenerate essential antioxidants and to repair important molecules damaged by oxidation. The largest part of the effects of ALA/DHLA couple can be explained by a specific stimulatory activity on Nrf2-dependent gene transcription and by the inhibition of NF-kappa B activity. These features have prompted its use as a drug for several diseases